Early Metabolic Changes with Thiazide or Beta Blocker Therapy for Essential Hypertension

ISRCTN ISRCTN06257223
DOI https://doi.org/10.1186/ISRCTN06257223
Secondary identifying numbers N0544160627
Submission date
30/09/2005
Registration date
30/09/2005
Last edited
17/04/2012
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Morris J Brown
Scientific

Box No 110
Dept. of Clinical Pharmacology
Addenbrooke's NHS Trust
Cambridge
CB2 2QQ
United Kingdom

Phone +44 (0)1223 762574
Email mjb14@medschl.cam.ac.uk

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific title
Study objectivesCan the oral glucose tolerance test detect changes after 4 weeks treatment with thiazide diuretics or beta blockers or combination of the two?
Ethics approval(s)Added 5 August 2008: approved by Cambridge Research Ethics Committee on
26/11/04.
Health condition(s) or problem(s) studiedHypertension
InterventionDrug(s) vs placebo.
Blood samples for glucose and insulin determination. Collected by Research team/CIW staff.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Atenolol, bendrofluazide
Primary outcome measureChange in 2 hour glucose between any drug/drug combination versus placebo.
Secondary outcome measuresAdded 5 August 2008:
1. Do patients show a similar change in glucose tolerance after thiazide or
beta blocker treatment?
2. Does the combination of drugs cause a greater reduction in glucose tolerance
than expected from the response to each drug alone?
Overall study start date01/02/2005
Completion date01/02/2008

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participantsPilot: 12, main study: 66
Key inclusion criteriaNon-diabetic patients who are diagnosed as having essential hypertension will be recruited.

We will be comparing the two most commonly used drugs to treat hypertension, atenolol and bendrofluazide, in patients for whom the drugs (and the doses to be used) are licenced.

We propose an initial open label pilot study of 10-12 patients to confirm final doses to be tested, the duration of therapy for optimum timing of the OGTT and tolerability of doses selected. The pilot study will also be used to confirm sample size calculations for the main study. The protocol for the pilot study will be identical to the main study, but there will not be a placebo phase and the treatment will not be blinded.

The main study will be double-blind, placebo controlled, cross-over study, of approximately 66 patients in which each patient receives in random order, 4 weeks treatment with either Bendrofluazide 5-10mg daily, Atenolol 50-100mg daily or combination of Bendrofluazide 2.5-5mg and Atenolol 25-50mg daily. There will be a forced titration from the lower to the higher dose stated half way through each dosing period. There will be a 1 month placebo wash-out between each dosing period.

At 0, 2 and 4 weeks of each treatment phase, patients will attend the Clinical Investigation Ward (CIW), fasting, for performance of an oral glucose tolerance test (OGTT). Blood will be drawn from an intravenous cannula, for the measurements of glucose and insulin at 0, 1 and 2 hours.

Blood pressure will be measured at each study visit using an Omron machine. The patients will also be given a blood pressure machine to take home and will be asked to measure and record their blood pressure at least twice per week. If their blood pressure is under 110/70mmhg or over 160/110mmHg at any time or if the patient has symptoms e.g. headache or dizziness, the patient will be asked to contact study staff. If the blood pressure remains over 160/110 for two measurements, then another antihypertensive therapy may be commenced, or the patient withdrawn from the study. If blood pressure is < 110/70 mmHg with symptoms then a decision may be made to terminate their participation in the study.

The doses of drugs to be used, while commonly used for angina and oedema, are higher than now commonly used for hypertension. We expect them to be well tolerated during short term use. These doses have also been chosen because they will enable genetic studies top be performed subsequently in a large number of patients.

Prof M Brown and Clinical Pharmacology Unit team has experience of many research studies in the treatment of hypertension. The design of this study has been derived partly from previous experience from these studies and from patient suggestions from these studies.
Key exclusion criteria1. Any patient already taking thiazide diuretics or beta blockers in whom these drugs cannot be switched to alternative drugs with similar or better blood pressure control.
2. Any patient who is intolerant of these medications will be excluded from the study.
Date of first enrolment01/02/2005
Date of final enrolment01/02/2008

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Box No 110
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Department of Health
Government

Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom

Phone +44 (0)20 7307 2622
Email dhmail@doh.gsi.org.uk
Website http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Government

Cambridge Consortium - Addenbrooke's (UK) - NHS Research and Development Support Funding

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/05/2012 Yes No